The Effects of Cocaine on Depressed Patients

Post, Robert M.; Kotin, Joel; Goodwin, Frederick K.

doi:10.1176/ajp.131.5.511

Cited by 166 publications

(22 citation statements)

References 22 publications

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“…Cocaine also reduced immobility in the FST, consistent with the antidepressant and "mood-elevating" effects of the drug (Post et al, 1974). Furthermore, cocaine increased swimming behaviors without affecting climbing behaviors.…”

Section: Discussionsupporting

confidence: 60%

Antidepressant-Like Effects of κ-Opioid Receptor Antagonists in the Forced Swim Test in Rats

Mague

Pliakas

Todtenkopf

et al. 2003

J Pharmacol Exp Ther

447

418

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We showed previously that cAMP response element-binding protein (CREB) within the nucleus accumbens (NAc) of rats regulates immobility in the forced swim test (FST), an assay used to study depression. Because CREB regulates expression of dynorphin (which acts at -opioid receptors) in NAc neurons, these findings raised the possibility that -receptors mediate immobility behaviors in the FST. Here, we report that i.c.v. administration of the -antagonist nor-binaltorphimine dose dependently decreased immobility in the FST, suggesting that it has antidepressant-like effects. Implicating a specific effect at -receptors, similar antidepressant-like effects were seen after treatment with either of two novel, structurally dissimilar -antagonists: 5Ј-guanidinonaltrindole, which was effective after i.c.v. but not systemic treatment, and 5Ј-acetamidinoethylnaltrindole (ANTI), which was potent and effective after systemic treatment. The behavioral effects of the -antagonists resembled those of tricyclic antidepressants (desipramine) and selective serotonin reuptake inhibitors (fluoxetine and citalopram). Conversely, systemic administration of the -agonist) dose dependently increased immobility in the FST, consistent with prodepressant-like effects. The effects of the -ligands in the FST were not correlated with nonspecific effects on locomotor activity. Furthermore, the most potent and effective -antagonist (ANTI) did not affect the rewarding impact of lateral hypothalamic brain stimulation at a dose with strong antidepressant-like effects. These findings are consistent with the hypothesis that CREB-mediated induction of dynorphin in the NAc "triggers" immobility behavior in the FST. Furthermore, they raise the possibility that -antagonists may have efficacy as antidepressants, but lack stimulant or rewardrelated effects.The neurobiology of depression is not understood. Because most antidepressants with clinical efficacy act upon monoamines [primarily norepinephrine (NE) and serotonin (5HT)], much research on depression has focused upon interactions between these neurotransmitters and their reuptake transporters and receptor proteins. However, recent research has become progressively focused upon the intracellular mechanisms of depression and antidepressant treatments (Manji et al., 2001;Duman, 2002;Nestler et al., 2002), with the goal of developing novel therapeutics that act faster, are more efficacious, and have fewer side effects. This approach has led to the study of brain circuits typically associated with reward-related processes, including the mesolimbic dopamine (DA) system Newton et al., 2002).The mesolimbic DA system projects from the ventral tegmental area of the midbrain to the nucleus accumbens (NAc) of the basal forebrain, and is modulated directly and indirectly by noradrenergic and serotonergic inputs (Pasquier et al., 1977). This circuitry contributes importantly to the hedonic (rewarding) effects of food, sexual behavior, and addictive drugs (Carlezon and Wise, 1996b;Kreek and Koob, 1998;Wise, 1998...

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Section: Discussionsupporting

confidence: 60%

Antidepressant-Like Effects of κ-Opioid Receptor Antagonists in the Forced Swim Test in Rats

Mague

Pliakas

Todtenkopf

et al. 2003

J Pharmacol Exp Ther

447

418

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“…Phencyclidine is classified with a question mark due to the fact that 57% of the n-profiles are classified as new, indicating that phencyclidine does not belong to this group. The clinically well-known antide pressant effect of psychostimulants, especially nrethylphenidate and cocaine, is seen in the overall results for this class [69][70][71], Amphetamine may be of help as an adjunct to antidepressant therapy [72], The success rate of the classification system in predicting psychostimulant activ ity of drugs is between 86 and 100%. The pharmacologi cal modes of action of amphetamine, methylphenidate, caffeine and pipradrol resemble each other as do their effects on the ECoG.…”

Section: Discussionmentioning

confidence: 99%

Classification of Psychotropic Drugs Based on Pharmaco-electrocorticographic Studies in Vigilance-Controlled Rats

1993

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The effects of a number of psycho-active drugs on electrocorticographic activity (ECoG) of the rat have been studied. Frontoparietal ECoG was recorded during 6-min periods immediately before drug/vehicle administration and starting at 20 and 45 min after administration. For each 6-min recording time, a mean power spectrum was calculated and smoothed. A quotient of the power at 20 and 45 min after and before drug, respectively, was then calculated. These quotients were used as input for an analysis of variance, followed by a t test and a normalization for the degrees of freedom, resulting in so-called n-profiles. Although each drug has its own characteristic n-profile, n-profiles of drugs belonging to the same clinical class have some characteristics in common. An automated classification system of psychotropic drugs, based on parameters extracted from n-profiles by discriminant analysis, is presented. For the antidepressant drug class the success rate of correct classification of antidepressant drugs is between 53 and 88%, for a neuroleptic drug in the neuroleptic drug class the success rate is 87%, for an anxiolytic drug in the anxiolytic drug class 100% and for a psychostimulant drug in the psycho-stimulant drug class between 86 and 100%. For a reliable classification of a drug about 10 n-profiles of active doses are needed. Using n-profiles, it appeared also possible to discriminate between antidepressant, neuroleptic, anxiolytic and psychostimulant drugs based on visual judgement. Moreover, visual evaluation of the n-profiles enables 4 subclasses to be recognized within the antidepressant class, 2 subclasses within the neuroleptic and 2 subclasses within the anxiolytic class.

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“…Use of cocaine as an antidepressant though, has not gained favor. Despite Freu d's conviction (5) that cocain e was an effective therapy for depression , t h is h as not been corroborated e xp e r ime nta lly in 10 depressed patients at the National Inst itute of Mental Health (6). Furthermore, Post noticed that coca ine is n ot o n ly ineffec tive as a treatment for depression but may also be capable of inducin g d ysphor ia (7).…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Pharmacologic Treatments of Cocaine Dependence

Knable¹

1989

JJP

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The Effects of Cocaine on Depressed Patients

Cited by 166 publications

References 22 publications

Antidepressant-Like Effects of κ-Opioid Receptor Antagonists in the Forced Swim Test in Rats

Antidepressant-Like Effects of κ-Opioid Receptor Antagonists in the Forced Swim Test in Rats

Classification of Psychotropic Drugs Based on Pharmaco-electrocorticographic Studies in Vigilance-Controlled Rats

Pharmacologic Treatments of Cocaine Dependence

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